Chronic uremia due to end stage renal disease in humans is associated with a significant morbidity and mortality. This syndrome is associated with a number of endocrine and metabolic disturbances. The principal objectives of the proposed investigations are the study of effects of altered endocrine regulations and chronic uremia on carbohydrate metabolism in patients with end stage renal disease. The already developed mass-spectrometric techniques for the use of stable non-radioactive tracers will be applied to the study of fuel metabolism in humans. These methods permit the use of chemically small quantities of substrates in humans without exceeding the isotopic abundance from that found in natural biological systems. From the point of view of clinical syndromes, these studies will evaluate the relationships between major body fuels. Quantification of these data will be helpful in better understanding of the metabolic perturbations in uremia and will aid in the development and testing of new treatment regimens.